In beta-cells, mitochondria integrate and generate metabolic signals controlling insulin secretion

• Published in: The international journal of biochemistry & cell biology Vol. 38; no. 5; pp. 696 - 709
• Main Authors: Maechler, Pierre, Carobbio, Stefania, Rubi, Blanca
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-01-2006
• Subjects: Adenosine Triphosphate - biosynthesis; Animals; Beta-cell; Diabetes Mellitus, Type 2 - physiopathology; Electron Transport Chain Complex Proteins - metabolism; Exocytosis - physiology; Glutamate dehydrogenase; Glutamate Dehydrogenase - metabolism; Humans; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - physiology; Insulin-Secreting Cells - ultrastructure; Mitochondria; Mitochondria - metabolism; NAD - metabolism; Pyruvic Acid - metabolism; Signal Transduction - physiology; Glutamate dehydrogenase; GLP-1; Beta-cell; BCH; GDH; GAD; Insulin secretion; Mitochondria; TCA; ROS; UCP2; LCPT1; K ATP-channel; AGC
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2005.12.006

Pancreatic beta-cells are unique neuroendocrine cells displaying the peculiar feature of responding to nutrients, principally glucose, as primary stimulus. This requires translation of a metabolic substrate into intracellular messengers recognized by the exocytotic machinery. Central to this signal transduction mechanism, mitochondria integrate and generate metabolic signals, thereby coupling glucose recognition to insulin secretion. In response to a glucose rise, nucleotides and metabolites are generated by mitochondria and participate, together with cytosolic calcium, to the stimulation of insulin exocytosis. This review describes the mitochondrion-dependent pathways of regulated insulin secretion. In particular, importance of cataplerotic and anaplerotic processes is discussed, with special attention to the mitochondrial enzyme glutamate dehydrogenase. Mitochondrial defects, such as mutations and reactive oxygen species production, are presented in the context of beta-cell failure in the course of type 2 diabetes.